Inflammatory corpuscle AIM2 facilitates macrophage foam cell formation by inhibiting cholesterol efflux protein ABCA1.

The inflammatory corpuscle recombinant absents in melanoma 2 (AIM2) and cholesterol efflux protein ATP binding cassette transporter A1(ABCA1) have been reported to play opposing roles in atherosclerosis (AS) plaques. However, the relationship between AIM2 and ABCA1 remains unclear. In this study, we explored the potential connection between AIM2 and ABCA1 in the modulation of AS by bioinformatic analysis combined with in vitro experiments. The GEO database was used to obtain AS transcriptional profiling data; screen differentially expressed genes (DEGs) and construct a weighted gene co-expression network analysis (WGCNA) to obtain AS-related modules. Phorbol myristate acetate (PMA) was used to induce macrophage modelling in THP-1 cells, and ox-LDL was used to induce macrophage foam cell formation. The experiment was divided into Negative Control (NC) group, Model Control (MC) group, AIM2 overexpression + ox-LDL (OE AIM2 + ox-LDL) group, and AIM2 short hairpin RNA + ox-LDL (sh AIM2 + ox-LDL) group. The intracellular cholesterol efflux rate was detected by scintillation counting; high-performance liquid chromatography (HPLC) was used to detect intracellular cholesterol levels; apoptosis levels were detected by TUNEL kit; levels of inflammatory markers (IL-1ß, IL-18, ROS, and GSH) were detected by ELISA kits; and levels of AIM2 and ABCA1 proteins were detected by Western blot. Bioinformatic analysis revealed that the turquoise module correlated most strongly with AS, and AIM2 and ABCA1 were co-expressed in the turquoise module with a trend towards negative correlation. In vitro experiments demonstrated that AIM2 inhibited macrophage cholesterol efflux, resulting in increased intracellular cholesterol levels and foam cell formation. Moreover, AIM2 had a synergistic effect with ox-LDL, exacerbating macrophage oxidative stress and inflammatory response. Silencing AIM2 ameliorated the above conditions. Furthermore, the protein expression levels of AIM2 and ABCA1 were consistent with the bioinformatic analysis, showing a negative correlation. AIM2 inhibits ABCA1 expression, causing abnormal cholesterol metabolism in macrophages and ultimately leading to foam cell formation. Inhibiting AIM2 may reverse this process. Overall, our study suggests that AIM2 is a reliable anti-inflammatory therapeutic target for AS. Inhibiting AIM2 expression may reduce foam cell formation and, consequently, inhibit the progression of AS plaques.

The efficacy and safety of the short-term combination therapy with ticagrelor and PPIs or H2RA in patients with acute STEMI who underwent emergency PCI.

Combination therapy with platelet inhibitors and acid-suppressive agents is recommended for patients with acute ST-segment elevation myocardial infarction (STEMI) who underwent percutaneous coronary intervention (PCI), but there remains a paucity of data to evaluate both the efficacy and safety of these combinations. In this prospective study, a total of 170 patients with acute STEMI who underwent PCI were divided into four groups: pantoprazole + ticagrelor, omeprazole + ticagrelor, ranitidine + ticagrelor, and ticagrelor only. The risk of PCI, antithrombotic efficacy, cardiac function, and main end points were evaluated and compared. No significant differences were found in infarction-related artery perfusion indexes (thrombolysis in myocardial infarction [TIMI], corrected TIMI frame count), the incidence of stent thrombosis after PCI, platelet indicators (platelet count, mean platelet volume, and platelet distribution width), platelet activation (P-selectin and glycoprotein IIb/IIIa levels), platelet aggregation (thrombelastography indicators, such as ADP% and MAADP ), myocardial necrosis biomarker (creatine kinase isoenzyme-MB and cardiac troponin I) levels, brain natriuretic peptide levels, the incidence of ischemic end point events, and the incidence of other tissue and organ bleeding events among the four groups. The incidence of gastrointestinal (GI) bleeding events in the proton pump-inhibitor (PPI) group was significantly lower than that in the control group, whereas in the H2 receptor antagonist (H2RA) group it was not significantly different from the control group. The short-term combination therapy with ticagrelor and PPIs or H2RA is safe and effective in patients with acute STEMI after PCI. In addition, the PPIs combined with ticagrelor could reduce the incidence of GI bleeding events without increasing the incidence of ischemic events.